Kidney and ureteral stones. Credit: Scientific Animations CC4.0
Sometimes all it takes is a little push. That is the conclusion of a study, published recently in the Journal of Urology, in which doctors used a handheld ultrasound device to nudge patients’ kidney-stone fragments.
As many as 50% of patients who have kidney stones removed surgically still have small fragments remaining in the kidneys afterward. Of those patients, about 25% find themselves returning for another operation within five years to remove the now-larger fragments.
UW Medicine researchers found, however, that patients who underwent the stone-moving ultrasound procedure had a 70% lower risk of such a recurrence.
“I think the main takeaways of this study are removing fragments reduces relapse and using a noninvasive, hand-held ultrasound device to help clear these kidney stone fragments,” said UW Medicine urologist Dr Jonathan Harper, the study’s senior author.
The multisite, randomised and controlled trial was conducted from May 2015 to April 2024. Almost all of the 82 participants were from the UW Medicine or the VA Puget Sound health systems. All had stone fragments that had persisted in their kidneys for months, and their ureters were free of stones and fragments.
In the study, 40 underwent ultrasound treatment to encourage fragments to clear from the kidneys, while 42 control-group members received no such treatment.
With patients awake in a clinic office setting, doctors used a wand that generated ultrasonic pulses through the skin to move the fragments closer to the ureter, where they could be naturally expelled, sometimes with the next urination, Harper noted.
Harper and his co-lead author on the paper, urologist Dr Mathew Sorensen, have worked on this technology and treatment for 15 years. They also use this technology, called burst wave lithotripsy, to blast larger stones into smaller pieces; those successes were published in 2022.
The pushing and breaking technologies are used with the same ultrasound platform.
Harper expressed hope that both clinical uses of the technology would become commonplace. A company, SonoMotion, is commercialising the technology, which was developed at the University of Washington, he added.
“I see a lot of potential in this It could become as common as getting your teeth cleaned. If you have a couple of small stones which could cause future problems, you make an office appointment and in 30 minutes you’re done.
“This could really revolutionise kidney stone treatment,” Harper said.
Higher thiazide doses are associated with greater reductions in urine calcium, which in turn correlate with fewer symptomatic kidney stone events, according to a Vanderbilt University Medical Center study out now in JAMA Network Open.
Thiazide diuretics, commonly prescribed to prevent kidney stone recurrence, are drugs that act directly on the kidneys to promote diuresis by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron. Thiazides are also used as a common treatment for high blood pressureand to clear fluid from the body in conditions such as heart failure.
First author Ryan Hsi, MD, FACS, associate professor in the Department of Urology at VUMC, said the study data help explain the findings of the multicentre Hydrochlorothiazide for Kidney Stone Recurrence Prevention (NOSTONE) trial, which reported that hydrochlorothiazide did not reduce recurrence of kidney stone events.
“In light of our research, the calcium reductions in that study were modest and likely insufficient to affect recurrence risk,” Hsi said.
“What this means for patients is that thiazides remain an important option in the toolkit for preventing kidney stone recurrence. It may be beneficial to monitor calcium excretion while on thiazide therapy to adjust dose and diet to attain an adequate reduction in urine calcium.”
A total of 634 participants were studied, revealing significant associations between higher thiazide doses and urine calcium reductions greater than those achieved in the NOSTONE trial, where participants took different doses of hydrochlorothiazide.
For next steps, the researchers are interested in understanding which subtypes of thiazides and their dosing work best, and how best to optimise medication adherence, since these therapies are often administered long term.
Type 2 diabetes is associated with increased risk of kidney stones, but some forms of treatment for this condition may also have the benefit of lowering risk of kidney stones. In a study led by investigators from Mass General Brigham, researchers found that there was an association between the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and a lower risk of developing kidney stones. Their findings are reported in JAMA Internal Medicine.
Rates of kidney stones are on the rise in the United States and around the world. Type 2 diabetes is associated with increased risk of kidney stones, but some forms of treatment for this condition may also have the benefit of lowering risk of kidney stones.
The study included data from three nationwide databases of patients with type 2 diabetes who were seen in routine clinical practice.
The team analysed information from 716,406 adults with type 2 diabetes who had started taking an SGLT2 inhibitor or two other classes of diabetes medications known as GLP1 receptor agonists or dipeptidyl peptidase 4 (DPP4) inhibitors.
Patients who began taking SGLT2 inhibitors had a 30% lower risk of developing kidney stones than those taking GLP1 agonists and about a 25% lower risk than those taking DPP4 inhibitors.
The findings were consistent across sex, race/ethnicity, history of chronic kidney disease and obesity.
“Our findings could help inform clinical decision making for patients with diabetes who are at risk for developing kidney stones,” said corresponding author Julie Paik, MD, ScD, MPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney) Medicine at Brigham and Women’s Hospital.
Julie M. Paik, Helen Tesfaye, Gary C. Curhan, Heidi Zakoul, Deborah J. Wexler, Elisabetta Patorno. Sodium-Glucose Cotransporter 2 Inhibitors and Nephrolithiasis Risk in Patients With Type 2 Diabetes. JAMA Internal Medicine, 2024; DOI: 10.1001/jamainternmed.2023.7660
A new ultrasonic technique developed for emergency kidney stone treatments on Mars may offer an option to move kidney stones out of the ureter with minimal pain and no anaesthesia, according to a new feasibility study published in The Journal of Urology.
In the procedure, the physician uses a handheld transducer placed on the skin to direct ultrasound waves towards the stone. Using ultrasound propulsion, the stones can then moved and repositioned to promote their passage, while burst wave lithotripsy (BWL) can break up the stone.
Unlike with the standard technique of shock wave lithotripsy, there is minimal pain according to lead author Dr M. Kennedy Hall, a UW Medicine emergency medicine doctor. “It’s nearly painless, and you can do it while the patient is awake, and without sedation, which is critical.”
The researchers hope that one day the procedure of moving or breaking up the stones could eventually be performed in a clinic or emergency room setting with this technology, Dr Hall added.
Ureteral stones can cause severe pain and are a common reason for emergency department visits. Most patients with ureteral stones are advised to wait to see if the stone will pass on its own. However, this observation period can last for weeks, with nearly one-fourth of patients eventually requiring surgery, Dr Hall noted.
Dr Hall and colleagues evaluated the new technique to meet the need for a way to treat stones without surgery.
The study was designed to test the feasibility of using the ultrasonic propulsion or using BWL to break up stones in awake, unanaesthetised patients, Dr Hall said.
The study recruited 29 patients; 16 received propulsion and 13 received propulsion and BWL. In 19 patients, the stones moved. In two cases, the stones moved out of the ureter and into the bladder.
Burst wave lithotripsy fragmented the stones in seven of the cases. At a two-week follow up, 18 of 21 patients (86%) whose stones were located lower in the ureter, closer to the bladder, had passed their stones. In this group, the average time to stone passage was about four days, the study noted.
One of these patients felt “immediate relief” when the stone was dislodged from the ureter, the study stated.
The next step would a clinical trial with a control group, which would not receive either BWL bursts or ultrasound propulsion, to evaluate the degree to which this new technology potentially aids stone passage, Dr Hall said.
Development of this technology first started five years ago, when NASA funded a study to see if kidney stones could be moved or broken up, without anaesthesia, on long space flights, such as the Mars missions. The technology has worked so well that NASA has downgraded kidney stones as a key concern.
“We now have a potential solution for that problem,” Dr Hall said.
A new study showed, during kidney stone removal procedures, leaving small asymptomatic stones behind significantly increases the risk of a patient’s relapse in the following five years. The study findings appear in the New England Journal of Medicine.
Typically, stones < 6mm in diameter that are not a procedure’s primary target are not removed but monitored, since ‘secondary’ stones have high rates of successful passage if they move into the ureter, explained Dr Mathew Sorensen, a urologist at the University of Washington School of Medicine and the study’s lead author.
“Before this study, the clinical views were pretty mixed on whether some of these stones should be treated,” he said. “Most clinicians would decide, based on the size of the stone, whether it hit the bar for treatment, and if it did not, you would often ignore the little stones.”
The researchers studied 75 patients who were treated at multiple institutions over 2015 to 2021. About half of the patients had only their large primary stone treated, while the others had primary and secondary stones removed. Relapse was defined as having to go to the emergency room or undergo an additional procedure due to a recurrence or if a follow-up CT scan showed that the secondary stones grew.
Removal of the secondary stones reduced the relapse rate by 82%, the researchers found, leading the authors to recommend that smaller stones should not be left behind.
“Results of our trial support the removal of small asymptomatic renal stones at the time of surgery with a larger stone,” their paper concluded. The authors noted that while removal of smaller stones could add to the procedure’s duration and cost, those costs would likely be less than those associated with a patient’s repeat procedure or visit to the emergency room. Some patients in the study visited the emergency department multiple times and then required surgery, the report noted.
Dr Sorensen said he would share the study results with colleagues with the hope of changing their sensibility toward smaller stones. Further study is needed to determine whether treatment of small stones alone is justified, as technology improves and the costs and risks of intervention diminish, he said.
“I think we have proven through this rigorous study that removal of the small asymptomatic stones is beneficial when feasible and in patients that are candidates to have all their stones treated in one procedure,” he noted. “Leaving the stones behind risk trouble in the future.”
Geologists with the tools of their trade. Image by photochur from Pixabay
Geology studies stones to help find minerals, predict earthquakes and more, but now their expertise has been tapped to understand kidney stones — how they form, why are some people more susceptible to them and can they be prevented?
In a new paper published in the journal Nature Reviews Urology, researchers described the geological nature of kidney stones, outlined the arc of their formation, introduced a new classification scheme and suggested possible clinical interventions.
“The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature,” Illinois geology professor Bruce Fouke said. “We are bringing together geology, biology and medicine to map the entire process of kidney stone formation, step by step. With this road map in hand, more effective and targeted clinical interventions and therapies can now be developed.”
Kidney stones affect in 10 adults in their lifetime and send half a million people in the United States to emergency rooms annually, according to the National Kidney Foundation. Yet little is understood about the geology behind how kidney stones form, Fouke said.
The team’s previous research found that kidney stones form in the same way as regular stones do: they don’t crystallise all at once, instead going through cycles of partial dissolution and reformation. Doctors had previously believed that they form suddenly and intact.
The research team described in detail the multiple phases kidney stones go through in forming, dissolving and re-forming, using high-resolution imaging technologies. Their findings defy the typical classification schemes doctors use, which are based on bulk analyses of the type of mineral and the presumed location of formation in the kidney. Instead, the researchers drew up a new classification scheme based on the phase of formation the stone is in, and the chemical processes it is undergoing.
“If we can identify these phase transformations, what makes one step to go to another and how it progresses, then perhaps we can intervene in that progression and break the chain of chemical reactions happening inside the kidney tissues before a stone becomes problematic,” said lead author Mayandi Sivaguru, assistant director of core facilities at the Carl R Woese Institute for Genomic Biology at Illinois.
One particularly revelatory finding was in the very beginnings of kidney stone formation. The stones start off as microspherules, tiny droplets of mineral, which merge to form larger crystals throughout kidney tissues. They are normally flushed out, but when they merge together and form larger stones that continue to grow, they can become excruciatingly painful and even deadly in some cases, Fouke said.
“Stone formation is part of a natural, healthy process within kidneys where these tiny mineral deposits are shuttled away and excreted from the body,” Fouke explained. “But then there is a tipping point when those same mineral deposits start to grow together too rapidly and are physically unable to leave the kidney.”
An example of agate, which shows similar formation characteristics to kidney stones. Image source: Leon Macapagal on Unsplash
As the stone goes through the formation process, more microspherules merge, lose their rounded shape and transform into much larger, perfectly geometric crystals. Stones go through multiple cycles of partially dissolving—shedding up to 50% of their volume—and then growing again, creating a signature pattern of layered crystals much like those of agates, coral skeletons and hot-spring deposits seen around the world.
“Looking at a cross-section of a kidney stone, you would never guess that each of the layers was originally a bunch of little balls that lined up and coalesced. These are revolutionary new ways for us to understand how these minerals grow within the kidney and provide specific targets for stone growth prevention,” Fouke said.
The researchers listed a number of possible clinical interventions and treatment targets derived from this extra knowledge on kidney stone formation. They hope that these options can be tried out, from drug targets to changes in diet or supplements that could disrupt the cascade of kidney stone formation, Sivaguru said.
To aid in this testing, Fouke’s group developed the GeoBioCell, a microfluidic cartridge that mimics the intricate internal structures of the kidney. The team hopes the device can contribute to research as well as clinical diagnostic testing and the evaluation of potential therapies, particularly for the more than 70% of kidney stone patients with recurring stones.
“Ultimately, our vision is that every operating room would have a small geology lab attached. In that lab, you could do a very rapid diagnostic on a stone or stone fragment in a matter of minutes, and have informed and individualized treatment targets,” Fouke said.
Journal information: Mayandi Sivaguru et al, Human kidney stones: a natural record of universal biomineralization, Nature Reviews Urology (2021). DOI: 10.1038/s41585-021-00469-x
